In-vivo indwelling implement

Abstract

An in-vivo indwelling implement (1) has a coil (10), and a fiber layer (30) that is disposed on the outer circumferential surface (12) of the coil (10) and contains fibers. The fibers contain a polymer material and a drug. The mass per coil unit length of the fiber layer (30) disposed in a proximal part (10P) of the coil (10) is less than the mass per coil unit length of the fiber layer (30) disposed in a distal part (10D) of the coil (10), or the fiber layer (30) is disposed in the distal part (10D) of the coil (10) and the fiber layer (30) is not disposed in the proximal part (10P) of the coil (10).

Description

Intra-biological implantable devices

[0001] This disclosure relates to an in vivo implantable device for forming an embolism in a blood vessel in a vascular diseased area.

[0002] Endovascular treatment is one of the treatment methods for vascular lesions such as aneurysms of the head and neck, arteriovenous malformations, arteriovenous fistulas, pulmonary vascular malformations, renal vascular malformations, and aneurysms of the renal arteries and abdominal arteries. In endovascular treatment, an in vivo implantable device containing coils for embolus formation is placed at the target site to promote thrombosis, thereby preventing, for example, the rupture of an aneurysm. Several to tens of coils are used in a single embolization procedure. Patent documents 1 to 3 disclose in vivo implantable devices in which coils hold medication.

[0003] U.S. Patent Application Publication No. 2007 / 299461, JP 2013-537046, JP 2015-195978

[0004] However, the in-vivo implantable devices described in Patent Documents 1 to 3 had room for improvement in terms of drug sustained release. Therefore, the problem to be solved by this disclosure is to provide an in-vivo implantable device that can enhance drug sustained release.

[0005] An in-vivo implantation device according to the first embodiment of the present disclosure that can solve the above problems is as follows: [1] An in-vivo implantation device comprising: a coil; and a fiber layer disposed on the outer circumferential surface of the coil and containing fibers, wherein the fibers contain a polymer material and a drug, and the mass per unit length of the coil of the fiber layer disposed in the proximal part of the coil is less than the mass per unit length of the coil of the fiber layer disposed in the distal part of the coil, or the fiber layer is disposed in the distal part of the coil and the fiber layer is not disposed in the proximal part of the coil.

[0006] Furthermore, the in-vivo implantation device according to the first embodiment is preferably any of the following [2] to [4]. [2] The in-vivo implantation device according to [1], further comprising a pusher disposed proximal to the coil in the longitudinal direction of the coil and pushing the coil distally, and a connecting portion connecting the proximal portion of the coil and the distal portion of the pusher, wherein the fiber layer is disposed distal to the distal end of the connecting portion. [3] The in-vivo implantation device according to [2], having a first portion in which the coil and the connecting portion overlap in the longitudinal direction, and in the first portion, the fiber layer is not disposed on the surface of the coil. [4] The in-vivo implantation device according to [2], wherein the in-vivo implantation device has a first portion in which the coil and the connecting portion are arranged to overlap in the longitudinal direction, and a second portion in the longitudinal direction from the distal end of the coil to the distal end of the first portion, and the mass per unit length of the fiber layer arranged in the second portion is greater than the mass per unit length of the fiber layer arranged in the first portion.

[0007] An in-vivo implantation device according to a second embodiment of the present disclosure that can solve the above problems is as follows: [5] An in-vivo implantation device comprising: a coil; a first fiber layer disposed on the outer circumferential surface of the coil and containing fibers; and a second fiber layer disposed proximal to the first fiber layer on the outer circumferential surface of the coil and containing fibers, wherein the fibers of the first fiber layer and the fibers of the second fiber layer each contain a polymer material and a drug, and the mass per unit length of the coil of the second fiber layer is less than the mass per unit length of the coil of the first fiber layer.

[0008] Furthermore, the in-vivo implantation device according to the first or second embodiment is preferably any of the following [6] to [7]. [6] The in-vivo implantation device according to any one of [1] to [5], wherein the fiber includes a core-sheath type fiber having a core and a sheath, the core contains the drug and the sheath contains the polymer material. [7] The in-vivo implantation device according to any one of [1] to [6], wherein the polymer material is a biodegradable polymer material.

[0009] In the in-vivo implantation devices according to the first and second embodiments, the fibers of the fiber layer contain the drug, which prevents the drug from detaching from the coil early in the procedure and improves the sustained release of the drug compared to cases where the drug is coated on the coil surface. Furthermore, while providing a fiber layer on the coil surface tends to make the coil harder, in the in-vivo implantation device according to the first embodiment, the mass per unit length of the coil of the fiber layer is less in the proximal part of the coil than in the distal part, or the fiber layer is not provided in the proximal part. This makes it easier to form a harder distal part of the coil, making it easier to use the distal part to find empty space within the aneurysm and place the coil deep within the aneurysm. As a result, the displacement of the coil from the parent vessel can be suppressed. In addition, the coil can be made more flexible in the proximal part than in the distal part, making it easier to fold and pack the coil into the aneurysm in the latter half of the implantation procedure. In the in-vivo implantation device according to the second embodiment, the mass per unit length of the coil of the second fiber layer is less than the mass per unit length of the coil of the first fiber layer. This makes it easier to form a rigid coil in the portion of the coil where the first fiber layer is located, and to use this portion to search for empty spaces within the aneurysm and place the coil deep within the aneurysm. As a result, the displacement of the coil from the parent vessel can be suppressed. In addition, the coil can be made more flexible in the portion where the second fiber layer is located compared to the portion where the first fiber layer is located, making it easier to fold and pack the coil into the aneurysm during the latter half of the implantation process.

[0010] Figure 1 is a schematic diagram of an in-vivo implantation device according to the first embodiment. Figure 2 is a side view (partial cross-sectional view) along the longitudinal direction of the coil of the in-vivo implantation device shown in Figure 1, showing the coil extended in a straight line. Figure 3 is a cross-sectional view showing the fiber layer of the in-vivo implantation device shown in Figures 2 and 3. Schematic diagram showing the fiber structure of the fiber layer. Figure 5 is a schematic diagram showing a modified example of the fiber structure. Figure 3 is a schematic diagram showing an enlarged view of the fiber layer. Schematic diagram of a fiber having a branched portion. Figure 3 is a side view (partial cross-sectional view) showing a modified example of the in-vivo implantation device shown in Figure 3. Figure 3 is a side view (partial cross-sectional view) showing a modified example of the in-vivo implantation device shown in Figure 3. Figure 4 is a side view (partial cross-sectional view) showing another modified example of the in-vivo implantation device shown in Figure 3. Figure 5 is a side view (partial cross-sectional view) showing yet another modified example of the in-vivo implantation device shown in Figure 3. Figure 6 is a side view (partial cross-sectional view) showing yet another modified example of the in-vivo implantation device shown in Figure 3. Figure 14 is a cross-sectional view (partially a side view) of the coil of the in-vivo implantation device according to the second embodiment, showing the coil extended in a straight line. Figure 14 is a side view (partially a cross-sectional view) showing a modified example of the in-vivo implantation device shown in Figure 14. Figure 14 is a side view (partially a cross-sectional view) showing another modified example of the in-vivo implantation device shown in Figure 14.

[0011] The contents of this disclosure will be described in more detail below based on the embodiments described below. However, the contents of this disclosure are not limited by the embodiments described below, and it is certainly possible to implement the disclosure with appropriate modifications within the scope that is consistent with the spirit of the preceding and following descriptions, and all such modifications are included within the technical scope of this disclosure. In addition, hatching and component reference numerals may be omitted in the drawings for convenience, in which case refer to the specification or other drawings. Furthermore, the dimensions of various components in the drawings may differ from the actual dimensions, as priority is given to helping to understand the features of this disclosure.

[0012] (First Embodiment) The in-vivo implantation device according to the first embodiment of the present disclosure comprises a coil and a fiber layer disposed on the outer circumferential surface of the coil, wherein the fiber contains a polymer material and a drug, and the mass per unit length of the coil of the fiber layer disposed in the proximal part of the coil is less than the mass per unit length of the coil of the fiber layer disposed in the distal part of the coil, or the fiber layer is disposed in the distal part of the coil and the fiber layer is not disposed in the proximal part of the coil. Hereinafter, the in-vivo implantation device may be simply referred to as the implantation device.

[0013] An implantable device is placed inside the body in minimally invasive treatments for lesions or abnormalities in blood vessels or the digestive tract, such as aneurysms, thrombi, stenosis, or occlusion. Preferably, the implantable device is for cerebral aneurysms. A cerebral aneurysm implantable device can be used in one of the framing, filling, or finishing phases, or it can be used across two or three of these phases.

[0014] The in-vivo implantation device according to the first embodiment will be described with reference to Figures 1 to 13. Figure 1 is a schematic diagram of the in-vivo implantation device according to the first embodiment. Figure 2 is a side view (partially a cross-sectional view) along the longitudinal direction of the coil of the in-vivo implantation device shown in Figure 1, showing the coil extended in a straight line. Figure 3 is a cross-sectional view (partially a side view) along the longitudinal direction of the coil of the in-vivo implantation device shown in Figure 1, showing the coil extended in a straight line. Figure 4 is a cross-sectional view showing the fiber layer of the in-vivo implantation device shown in Figures 2 to 3. Figure 5 is a schematic diagram showing the fiber structure of the fiber layer. Figure 6 is a schematic diagram showing a modified example of the fiber structure shown in Figure 5. Figure 7 is a schematic diagram of an enlarged view of the fiber layer. Figure 8 is a schematic diagram of a fiber having a branched portion. Figures 9 to 13 are side views (partially a cross-sectional view) showing yet another modified example of the in-vivo implantation device shown in Figure 3. In Figure 1, the fiber layer 30 is omitted to facilitate understanding of the shape of the secondary coil. Although only the coil 10 and fiber layer 30 are shown in Figures 12 and 13, it is preferable that other components are arranged as in Figures 2 and 3. As shown in Figures 2 and 3, the retaining device 1 has a coil 10 and a fiber layer 30.

[0015] As can be seen from Figures 2 and 3, the coil 10 preferably has a longitudinal direction x, a radial direction y, and a circumferential direction z. The longitudinal direction x can also be called the longitudinal axis direction. The coil 10 preferably has a distal end and a proximal end in the longitudinal direction x. The proximal side of the coil 10 refers to the direction toward the user or operator's hand with respect to the longitudinal direction x of the coil 10, and the distal side refers to the opposite direction from the proximal side, i.e., the direction toward the treatment target. In Figures 2 and 3, the right side of the figure is the proximal side, and the left side of the figure is the distal side. The radial direction y of the coil 10 refers to the radial direction of the coil 10, and in the radial direction y, inward refers to the direction toward the center of the longitudinal axis of the coil 10, and outward refers to the direction extending radially from the center of the longitudinal axis on the opposite side from the inward direction. The circumferential direction z of the coil 10 refers to the direction around the longitudinal axis. In the following, when the length of each component of the coil 10 is divided into two equal parts in the longitudinal direction x, the proximal side may be referred to as the proximal portion, and the distal side as the distal portion.

[0016] As shown in Figure 3, the coil 10 has an outer circumferential surface 12. Preferably, the coil 10 has an inner circumferential surface 13. The surface of the coil 10 includes the outer circumferential surface 12 and the inner circumferential surface 13. Preferably, the coil 10 has a lumen 11 that extends in the longitudinal direction x. The outer circumferential surface 12 of the coil 10 faces the outside of the coil 10, i.e., the outside in the radial direction y, and the inner circumferential surface 13 of the coil 10 faces the lumen 11. Preferably, a stretch resistance member 50, which will be described later, is placed in the lumen 11.

[0017] As shown in Figures 1 to 3, the coil 10 is constructed by winding a wire 21. Preferably, the coil 10 is constructed by winding a long wire 21. Preferably, the coil 10 is constructed by winding one or more wires 21 in a spiral shape. Examples of wires 21 include single wires, stranded wires, and coiled wires, with single wires being preferred. Furthermore, it is preferable that the wire 21 is not a coiled wire.

[0018] The wire 21 is preferably biocompatible and flexible. Examples of materials constituting the wire 21 include platinum, gold, titanium, tungsten and their alloys, stainless steel, and other metallic materials or combinations thereof. Among these, it is more preferable that the wire 21 is composed of a platinum-tungsten alloy.

[0019] As shown in Figure 2, the wire 21 has a longitudinal axis direction p, and has a distal end and a proximal end in the longitudinal axis direction p. The wire 21 may be composed of a single wire from the distal end to the proximal end, or it may be composed of multiple wires connected to each other in the longitudinal axis direction p. The shape of the cross section perpendicular to the longitudinal axis direction p of the wire 21 may be circular, oval, polygonal, or a combination thereof. The shape of the cross section perpendicular to the longitudinal axis direction p of the wire 21 may be the same throughout the entire longitudinal axis direction p of the wire 21, or it may differ depending on the position in the longitudinal axis direction p.

[0020] The outer diameter of the wire 21 is not particularly limited, but may be, for example, 25 μm or more, 30 μm or more, or 35 μm or more, and may be 75 μm or less, or 70 μm or less.

[0021] The outer diameter of the wire 21 may be the same in the longitudinal axis direction p of the wire 21, or it may be different depending on the position in the longitudinal axis direction p of the wire 21. If the cross-section of the wire 21 is not circular, the outer diameter of the wire 21 shall refer to the diameter equivalent to a circle.

[0022] The coil 10 may be a single-layer coil or a multi-layer coil having multiple layers. A portion of the coil 10 in the longitudinal direction x may be a single layer, and the remaining portion may be multi-layer.

[0023] The density of the coil 10, i.e., the winding spacing, is not particularly limited and can be tightly wound, pitched, or a combination of these. The coil 10 may have adjacent wires 21 in contact with each other in the longitudinal direction x. The coil 10 may have adjacent wires 21 in contact with each other in only a part of the longitudinal direction x, or adjacent wires 21 in contact with each other throughout the entire longitudinal direction x. Furthermore, the coil 10 may not have adjacent wires 21 in contact with each other in the longitudinal direction x. The state of not being in contact means that there is a gap between adjacent wires 21 in the longitudinal direction x of the coil 10.

[0024] The outer edge shape of the cross-section perpendicular to the longitudinal direction x of the coil 10 may be circular, oval, polygonal, or a combination thereof. The oval shape includes elliptical, egg-shaped, and rounded rectangular shapes. The same applies in the following description.

[0025] The surface of the coil 10 may have an uneven surface structure if the cross-sections of adjacent wires 21 in the longitudinal direction x of the coil 10 are circular, elliptical, or the like.

[0026] The maximum and minimum outer diameters of the coil 10 are not particularly limited and can be appropriately selected according to the phase of the procedure. For example, they may be 150 μm or more, 180 μm or more, or 200 μm or more, and may also be 400 μm or less, 380 μm or less, or 350 μm or less.

[0027] The outer diameter and / or inner diameter of the coil 10 may be the same size in the longitudinal direction x of the coil 10, or they may be different sizes depending on the position in the longitudinal direction x of the coil 10. If the cross-section of the coil 10 is not circular, the outer diameter of the coil 10 shall refer to the equivalent diameter of a circle. Similarly, if the inner lumen cross-section of the coil 10 is not circular, the inner diameter of the coil 10 shall refer to the equivalent diameter of a circle.

[0028] The coil 10 may have a constant outer diameter in the longitudinal direction x. A constant outer diameter means that the outer diameter of the coil 10 is substantially constant over the entire longitudinal direction x, and includes cases where the change in the outer diameter of the coil 10 over the entire longitudinal direction x is within ±5%.

[0029] As shown in FIGS. 2 to 3, the indwelling device 1 is arranged on the outer peripheral surface 12 of the coil 10 and has a fiber layer 30 containing fibers 40.

[0030] The fiber layer 30 may be arranged only on a part of the outer peripheral surface 12 of the coil 10, or may be arranged on the entire outer peripheral surface 12 of the coil 10. The fiber layer 30 may be arranged on the inner peripheral surface 13 of the coil 10. The fiber layer 30 may be arranged only on a part of the inner peripheral surface 13 of the coil 10, or may be arranged on the entire inner peripheral surface 13 of the coil 10.

[0031] As shown in FIGS. 2 to 3, it is preferable that the fiber layer 30 has a cylindrical shape arranged along the peripheral wall of the coil 10. As shown in FIG. 4, it is preferable that the fiber layer 30 has a cylindrical shape with only one lumen 31. As can be understood from FIG. 3, it is preferable that the axial center in the longitudinal direction x of the coil 10 overlaps with the axial center in the longitudinal direction of the cylindrical fiber layer 30.

[0032] When the fiber layer 30 has a cylindrical shape, it is preferable that the fiber layer 30 has an outer peripheral surface 32 facing the outside of the indwelling device 1 and an inner peripheral surface 33 facing the outer peripheral surface 12 side of the coil 10. It is preferable that the fiber layer 30 has a distal end 34 and a proximal end 35 in the longitudinal direction x.

[0033] As can be understood from FIGS. 2 to 3, it is preferable that the inner peripheral surface 33 of the fiber layer 30 is in contact with the outer peripheral surface 12 of the coil 10. In the radial direction y, it is preferable that no other member is arranged between the coil 10 and the fiber layer 30. For example, it is preferable that no drug is applied to the outer peripheral surface 12 of the coil 10 in a form other than the fiber layer 30.

[0034] The fiber layer 30 may be composed of a single layer or may be composed of a plurality of layers.

[0035] The fiber layer 30 may be fixed to the coil 10. The fixing method is not particularly limited, and examples thereof include sewing, adhesion, welding, clamping, and the like. The fiber layer 30 may be fixed to the coil 10 by a part of the fiber layer 30 being sandwiched between two wire materials 21 constituting the coil 10. The fiber layer 30 may be fixed by the inner peripheral surface 33 of the fiber layer 30 being adhered or welded to the outer peripheral surface 12 of the coil 10.

[0036] In the fiber layer 30, the fiber 40 may be wound around the outer peripheral surface 12 of the coil 10. That is, in the fiber layer 30, the fiber 40 may be wound around the axis in the longitudinal direction x of the coil 10.

[0037] Only one fiber layer 30 may be arranged on the coil 10, or a plurality of fiber layers 30 may be arranged. The plurality of fiber layers 30 are preferably arranged side by side in the longitudinal direction x. The plurality of fiber layers 30 may be spaced apart from each other or in contact with each other in the longitudinal direction x. The plurality of fiber layers 30 preferably all have a cylindrical shape.

[0038] As shown in the image 60 of FIG. 7, the fiber layer 30 includes the fiber 40. Generally, a fiber is a thin filamentous substance, but in this specification, the fiber 40 refers to those having an average fiber diameter of 100 μm or less, and those having an average fiber diameter exceeding 100 μm are excluded. The average fiber diameter of the fiber 40 can be measured by the following method. Using a scanning electron microscope or a laser microscope (for example, a scanning transmission electron microscope (STEM-EDX / EELS) HD-2700 manufactured by Hitachi High-Technologies Corporation), an image of the fiber at a magnification of 1000 times is obtained. The arithmetic mean value of the diameters of at least 20 fibers measured in the obtained image is taken as the average fiber diameter of the fiber 40. When measuring the diameter of the fiber, in the case of a non-circular cross-sectional shape of the fiber, the average value of the diameters of the circumscribed circle and the inscribed circle of the non-circular cross-section is taken as the diameter of the fiber.

[0039] As shown in FIGS. 5 to 6, in the indwelling device 1, since the fiber layer 30 includes the fiber 40 containing the polymer material 41 and the drug 42, compared with the case where the drug is applied to the coil surface, it can prevent the drug from falling off from the coil 10 at an early stage of the procedure and can enhance the drug sustained release property.

[0040] As the fiber layer 30, a sheet-like or tubular fiber assembly composed of fibers 40 can be used. The fiber assembly may be a knitted fabric, woven fabric, nonwoven fabric, etc., formed from the fibers 40, and the nonwoven fabric may be a dry-laid nonwoven fabric or a wet-laid nonwoven fabric. In the fiber assembly, the fibers 40 may be joined to each other physically, chemically, or mechanically. In the fiber layer 30, the fibers 40 may be joined to each other by entanglement, or they may be joined by heat fusion.

[0041] The fiber layer 30 can be composed of one or more fibers 40. The fibers 40 may be composed of fiber bundles of multiple fibers. The form of the fiber bundle is not particularly limited and may be twisted, untwisted, or untwisted. The number of fibers in the fiber bundle may be, for example, two to ten.

[0042] The fiber layer 30 may be composed of only one type of fiber 40. For example, the fiber layer 30 may be composed only of fibers containing a biodegradable polymer material and a drug, or it may be composed only of fibers containing a non-biodegradable polymer material and a drug.

[0043] The fiber layer 30 may be composed of multiple types of fibers 40. For example, the fiber layer 30 may be composed of a first fiber containing a biodegradable polymer material and a drug, and a second fiber containing a non-biodegradable polymer material and a drug.

[0044] The fiber 40 may be a hollow fiber, but it is preferable that it be a solid fiber. The fiber 40 may or may not have crimp. A crimped fiber is, for example, a solid fiber having a spiral-shaped three-dimensional crimp structure.

[0045] A single fiber 40 may have a straight, linear shape, or it may have a branched shape, as shown in Figure 8. Figure 8 shows an example in which the fiber 40 has a branched portion 46, and the branched portion 46 has a first branch 46a and a second branch 46b.

[0046] The fiber layer 30 may stretch in the radial direction y. For example, as the coil 10 expands, the fiber layer 30 may stretch in the radial direction y.

[0047] The average fiber diameter of the fiber 40 is preferably 1 nm or more, 10 nm or more, 100 nm or more, or 1 μm or more. In order to prevent the outer diameter of the fiber layer 30 from becoming excessively large, the average fiber diameter of the fiber 40 is preferably 50 μm or less, 45 μm or less, or 40 μm or less.

[0048] The average fiber length of the fiber 40 may be, for example, 100 mm or more, 200 mm or more, 300 mm or more, or 1300 mm or less, 1200 mm or less, 1100 mm or less, or 1000 mm or less.

[0049] (Method for measuring the average fiber length of a fiber) Ten arbitrary single fibers are taken from the fiber layer 30. Each fiber is straightened without stretching, and its fiber length (mm) is measured on a measuring scale. The average of the measured fiber lengths of the ten fibers is taken as the average fiber length of fiber 40. If the number of fibers constituting the fiber layer is less than ten, the fiber length of all the fibers constituting the fiber layer is measured, and the average of the measured fiber lengths is taken as the average fiber length of fiber 40. If the number of fibers constituting the fiber layer is one, the fiber length of that one fiber is taken as the average fiber length of fiber 40. As shown in Figure 8, if the fiber 40 to be measured has a branching portion 46, and for example the branching portion 46 has a first branch 46a and a second branch 46b, the longer of the first branch 46a and the second branch 46b (first branch 46a in Figure 8) is used to calculate the fiber length.

[0050] The fibers 40 can be formed using, for example, electrospinning, melt spinning, wet spinning, or dry spinning, and among these, it is preferable to form them using electrospinning. When forming the fiber layer 30 by electrospinning, a coil 10 is used as a collector in the electrospinning system, and the fibers 40 can be wound around the outer surface of the coil 10 by spinning while rotating the coil 10.

[0051] Preferably, the fiber layer 30 does not contain any materials other than the fibers 40, such as thread-like materials with an average fiber diameter of more than 100 μm, resin wires, metal wires, etc.

[0052] Preferably, the fiber layer 30 is composed only of fibers 40 containing a polymer material 41 and a drug 42.

[0053] The polymer contained in the polymer material 41 may be a synthetic polymer or a natural polymer. The polymer material 41 also includes resins.

[0054] The polymer material 41 contained in the fiber 40 is preferably a biodegradable polymer material. As the biodegradable material decomposes, the surface area of ​​the fiber 40 tends to increase, making it easier to release the drug 42 contained in the fiber 40. In this specification, a biodegradable polymer material refers to a material that has the property of being hydrolyzed in the body environment and, after decomposition, becomes a non-toxic low-molecular-weight substance that is metabolized.

[0055] The polymers contained in biodegradable polymer materials may be synthetic polymers or natural polymers, but synthetic polymers are preferred. Biodegradable polymer materials also include biodegradable resins. Examples of biodegradable polymer materials include polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), glycolic acid-lactide copolymer (PLGA), glycolic acid-ε-caprolactone copolymer, lactide-ε-caprolactone copolymer, glycolic acid-lactide-ε-caprolactone copolymer, poly(p-dioxanone) (PDO), poly(2-oxetanone), polymalic acid, polyhydroxyalkanoic acid (PHA), polyhydroxybutyrate (PHB), and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHH Examples of these substances include, but are not limited to, BV, poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBH), starches (carboxymethyl starch, dialdehyde starch), celluloses (CMC, MC, HEC, HPC), proteins (collagen, gelatin, glue, mixture of collagen and elastin), polysaccharides (glycosaminoglycans, chitin, chitosan, hyaluronic acid), gums (acacia gum, guar gum, tragacanth gum), fibroin, laminin, casein, polypeptides, tannins, lignin, alginic acid, etc. These may be used individually or in combination of two or more.

[0056] The polymer material 41 contained in the fiber 40 may be a non-biodegradable polymer material. This makes it less likely to decompose compared to the case of a biodegradable material, thus delaying the release timing of the drug 42 contained in the fiber 40. In this specification, a non-biodegradable polymer material refers to a material other than a biodegradable polymer material that is resistant to hydrolysis in the internal environment of the body.

[0057] The polymers contained in non-biodegradable polymer materials may be synthetic polymers or natural polymers, but synthetic polymers are preferred. Non-biodegradable polymer materials also include non-biodegradable resins. Examples of non-biodegradable polymer materials include, but are not limited to, vinyl acetate such as ethylene vinyl acetate, polyolefins such as polyethylene and polypropylene, polyesters such as polyethylene terephthalate, polyamides such as nylon, fluorine such as polyvinylidene fluoride and polytetrafluoroethylene, vinyl chloride such as acrylic and polyvinyl chloride, polycarbonate, epoxy, polyurethanes such as polyurethane elastomers, polyacrylonitrile, keratin, and silk fibroin. These may be used individually or in combination of two or more.

[0058] In addition to the materials described above, the polymer material 41 may also contain various additives such as plasticizers, pigments, flame retardants, antistatic agents, lubricants, softeners, surfactants, and antibacterial agents.

[0059] The drug 42 contained in the fiber 40 may be the active ingredient (API) alone, or it may be a mixture with other additives. Preferred additives include base materials, plasticizers, stabilizers, surfactants, and the like.

[0060] The type of drug 42 contained in the fiber 40 is not particularly limited as long as it is necessary for the prevention or treatment of the affected area. Preferably, the drug 42 has at least one of the following effects: anti-inflammatory effect, antioxidant effect, antihypertensive effect, vasoconstriction inhibitory effect, anticoagulant effect, and shear stress sensing inhibitory effect, and more preferably, it has at least one of the following effects: anti-inflammatory effect, antioxidant effect, antihypertensive effect, and vasoconstriction inhibitory effect. Examples of drugs include selective serotonin reuptake inhibitors (SSRIs) (fluoxetine, sertraline, paroxetine, etc.), DPP-4 inhibitors (sitagliptin, linagliptin, alogliptin, etc.), HMG-CoA reductase inhibitors (atorvastatin, pitavastatin, rosuvastatin, pravastatin, simvastatin, fluvastatin, lovastatin, mevastatin, cerivastatin, etc.), nonsteroidal anti-inflammatory drugs (NSAIDs) (ibuprofen, naproxen, celecoxib, etc.), angiotensin II receptor blockers (ARBs) (losartan, valsartan, telmisartan, etc.), tocopherol acetate (vitamin E acetate, eviprostat, estrol, etc.), ascorbic acid (Asconal, Cinal, Cefylol), and edaravone (Radicut, Free Radical Scavenger). Examples include anticoagulants (such as Jar), ​​N-acetyl-L-cysteine ​​(NAC), calcium channel blockers (such as amlodipine, nifedipine, and diltiazem), diuretics (such as furosemide, trichlormethiazide, and spironolactone), angiotensin-converting enzyme inhibitors (ACEs) (such as enalapril, lisinopril, and perindopril), beta-blockers (such as metoprolol, atenolol, and bisoprolol), alpha-blockers (such as prazosin, terazosin, and doxazosin), alpha-beta-blockers (such as carvedilol, labetalol, and butoxamine), nitrates (such as nitroglycerin and isosorbide dinitrate), prostacyclin analogs (such as epoprostenol and treprostinil), anticoagulants (such as heparin, heparin derivatives, warfarin, antithrombin drugs such as dabigatran, and rivaroxaban), and antiplatelet agents (such as aspirin, clopidogrel, and ticagrelor).

[0061] The drug 42 may be encapsulated in a capsule. The size of the capsule is preferably 10 nm or larger, more preferably 50 nm or larger, even more preferably 100 nm or larger, and also preferably 500 nm or smaller, more preferably 400 nm or smaller, and even more preferably 200 nm or smaller. The capsule is preferably made of a biodegradable material. As the biodegradable material, bioabsorbable polymers, natural polymers, decellularized biological tissues or cells, or combinations thereof can be used. As bioabsorbable polymers, at least one of polylactic acid (PLA), poly-L-lactic acid (PLLA), polyglycolic acid (PGA), copolymer of lactic acid and glycolic acid (PLGA), polycaprolactone (PCL), and polydioxanone (PDS) is preferably used. As natural polymers, at least one of collagen, laminin, fibroin, gelatin, glycosaminoglycan, chitin, chitosan, hyaluronic acid, and polypeptide is preferably used.

[0062] The fiber layer 30 may contain biodegradable materials other than the polymer material 41. Examples of such materials include biodegradable alloys such as magnesium alloys and iron-manganese alloys. A portion of the fiber 40 may be composed of a biodegradable alloy.

[0063] The fiber 40 may contain an X-ray opaque material. For example, the X-ray opaque material may be coated on the surface of the fiber 40, embedded within the fiber 40, or retained within the fiber 40. Examples of X-ray opaque materials include lead, barium, iodine, tungsten, gold, silver, platinum, iridium, platinum-iridium alloy, stainless steel, titanium, cobalt-chromium alloy, palladium, tantalum, and the like.

[0064] In addition to the materials mentioned above, the fiber 40 may also contain various additives such as plasticizers, pigments, flame retardants, antistatic agents, lubricants, softeners, and surfactants.

[0065] As shown in Figure 5, it is preferable that the polymer material 41 and the drug 42 are mixed in the fiber 40. The drug 42 may be dispersed in the polymer material 41 in the fiber 40. The drug 42 may be uniformly dispersed in the polymer material 41 or dispersed locally. The drug 42 may be dispersed in the polymer material 41 in particulate form. The drug 42 may be exposed on the surface of the fiber 40 or may be present only inside the fiber 40. In the fiber 40, the polymer material 41 may function as a matrix. In the fiber 40, the drug 42 may be dissolved in the polymer material 41.

[0066] The fiber 40 shown in Figure 5 can be produced, for example, by mixing (preferably kneading) a polymer material and a chemical agent. For production, a spinning system equipped with an extruder and a spinneret may be used, for example. The polymer material and chemical agent are mixed (preferably kneaded) in the extruder, the mixture is melted, and the mixture is extruded from the spinneret to produce the fiber.

[0067] In the fiber 40, the mixing ratio of polymer material 41 to drug 42 is preferably 1 / 1 or more by mass, more preferably 2 / 1 or more, even more preferably 3 / 1 or more, and also preferably 100 / 1 or less, more preferably 80 / 1 or less, and even more preferably 50 / 1 or less.

[0068] In the fiber 40, the content of the polymer material 41 is preferably 20 wt% or more, more preferably 30 wt% or more, even more preferably 40 wt% or more, preferably 80 wt% or less, more preferably 70 wt% or less, and even more preferably 60 wt% or less.

[0069] In the fiber 40, the content of the agent 42 is preferably 20 wt% or more, more preferably 30 wt% or more, even more preferably 40 wt% or more, preferably 80 wt% or less, more preferably 70 wt% or less, and even more preferably 60 wt% or less.

[0070] In the fiber 40, when the drug 42 is dispersed in particulate form within the polymer material 41, the particle size is not particularly limited, but may be, for example, 10.0 nm or larger, 50.0 nm or larger, 100 nm or larger, or 200 nm or larger. Alternatively, the particle size may be 5.00 μm or smaller, 4.00 μm or smaller, 3.00 μm or smaller, 2.00 μm or smaller, or 1.00 μm or smaller. Having the particle size within the above range makes it easier to uniformly disperse the particulate drug 42 in the polymer material 41, and also facilitates the manufacture of the fiber 40. Here, "particle size" refers to the volume-average particle size (D50) at the median 50% diameter in the particle size distribution obtained by dynamic light scattering or the like. Commercially available particulate drugs may be used, in which case the particle size listed in the catalog can be adopted.

[0071] The fiber 40 may be a composite fiber having a core-sheath structure, a side-by-side structure, or a sea-island structure. The core-sheath structure includes a concentric core-sheath structure and an eccentric core-sheath structure. In order to slow down the release rate of the active ingredient of the drug 42 from the fiber 40, it is preferable that the drug 42 is encapsulated in the polymer material 41 in the fiber 40. Encapsulating the drug 42 in the polymer material 41 means that the drug 42 is covered by the polymer material 41 and is not exposed to the outside. By covering the drug 42 with the polymer material 41, the occurrence of an initial burst of the drug 42 can be suppressed, and the release rate of the active ingredient of the drug 42 can be easily controlled.

[0072] As shown in Figure 6, the fiber 40 preferably includes a core-sheath type fiber having a core portion 44 and a sheath portion 45, and more preferably consists of a core-sheath type fiber. In that case, it is preferable that the core portion 44 contains the drug 42 and the sheath portion 45 contains a polymer material 41. By using a composite fiber of this shape, it becomes easier to suppress the occurrence of an initial burst of the drug 42 and to control the release rate of the active ingredient of the drug 42.

[0073] If the fiber 40 is a core-sheath type fiber having a core portion 44 and a sheath portion 45, and the fiber 40 is branched into a first branch portion 46a and a second branch portion 46b, then the core portion 44 may be exposed in the first branch portion 46a and / or the second branch portion 46b without being covered by the sheath portion 45.

[0074] In the core portion 44, the content of the polymer material 41 is preferably 20 wt% or less, more preferably 10 wt% or less, even more preferably 5 wt% or less, and it is even more preferable that the core portion 44 does not contain the polymer material 41.

[0075] In the sheath portion 45, the content of the drug 42 is preferably 20 wt% or less, more preferably 10 wt% or less, even more preferably 5 wt% or less, and it is even more preferable that the sheath portion 45 does not contain the drug 42.

[0076] The fiber layer 30 is preferably composed of one or more core-sheath type fibers.

[0077] To facilitate control of the release rate of the active ingredient in the drug, a concentric core sheath type structure is preferred for the composite fiber.

[0078] The core-sheath type fiber contained in fiber 40 can be manufactured in the same manner as general core-sheath type fibers. For manufacturing, for example, an electrospinning system equipped with a spinneret and collector having a multi-tube shape may be used. Preferably, the core material supplied to the system contains a drug 42, and the sheath material contains a polymer material 41. The core material may contain a solvent that is soluble in the drug 42. The sheath material may also contain a solvent that is soluble in the polymer material 41. The solvent is not particularly limited as long as it can dissolve the polymer material 41 and / or the drug 42 and can be sprayed from the spinneret. Examples of solvents include water, N,N-dimethylformamide (DMF), ethanol, acetone, tetrahydrofuran, chloroform, dichloromethane, ethyl acetate, toluene, and the like.

[0079] In the implantation device 1, as can be seen from Figure 3, the mass Mp per unit length of the fiber layer 30 located at the proximal portion 10P of the coil 10 is less than the mass Md per unit length of the fiber layer 30 located at the distal portion 10D of the coil 10, or, as shown in Figure 9, the fiber layer 30 is located at the distal portion 10D of the coil 10, but not at the proximal portion 10P of the coil 10. Providing a fiber layer 30 on the coil surface tends to make the coil 10 harder, but in the implantation device 1, the mass per unit length of the fiber layer 30 is less at the proximal portion 10P than at the distal portion 10D of the coil 10, or the fiber layer 30 is not located at the proximal portion 10P. This makes it easier to form a harder distal portion 10D of the coil 10, making it easier to use the distal portion 10D to find empty space within the aneurysm and place the coil 10 deep within the aneurysm. As a result, the displacement of the coil 10 from the parent vessel can be suppressed. Furthermore, the coil 10 can be made more flexible in the proximal portion 10P compared to the distal portion 10D, making it easier to fold and pack the coil 10 into the tumor during the latter half of the implantation process. Note that "stiff coil 10" means that the coil 10 has high bending rigidity.

[0080] The mass Mp per unit length of the fiber layer 30 located in the proximal portion 10P of the coil 10 can be expressed by the following formula (1). The mass Md per unit length of the fiber layer 30 located in the distal portion 10D of the coil 10 can be expressed by the following formula (2). Mp = mp (mg) / L1 (mm) ... (1) Md = md (mg) / L2 (mm) ... (2) Here, mp: the total mass of the fiber layer 30 located in the proximal part 10P of the coil 10, L1: the total length in the longitudinal direction x of the fiber layer 30 in the part corresponding to the proximal part 10P of the coil 10 when the fiber layer 30 is located in the coil 10, md: the total mass of the fiber layer 30 located in the distal part 10D of the coil 10, L2: the total length in the longitudinal direction x of the fiber layer 30 in the part corresponding to the distal part 10D of the coil 10 when the fiber layer 30 is located in the coil 10. Figure 3 shows L1 and L2.

[0081] The mass Mp per unit length of the fiber layer 30 located in the proximal part 10P of the coil 10 and the mass Md per unit length of the fiber layer 30 located in the distal part 10D of the coil 10 can be measured by the following method. (Method for measuring the mass of the fiber layer per unit length of the coil) Under standard conditions (temperature 23±2℃, relative humidity 50±5%), the lengths L1 and L2 are measured using a straight ruler (Shinwa Sokutei Co., Ltd., model 13005). At the midpoint 14 in the longitudinal direction x of the coil 10, the coil 10 is cut along the radial direction y by 1 cm using precision nippers (ESD Co., Ltd., model EA535TA-13) to separate the coil 10 into the proximal part 10P and the distal part 10D. The proximal part 10P is designated as test piece A1 and the distal part 10D as test piece A2. Test specimen A1 is immersed in deionized water, and the fiber layer 30 is scraped off from the proximal part 10P of the coil 10 using a blade such as a razor. Similarly, test specimen A2 is immersed in deionized water, and the fiber layer 30 is scraped off from the distal part 10D of the coil 10 using a blade such as a razor. By scraping the fiber layer 30 from the coil 10 in deionized water in a way that removes fragments of the fibers 40 of the fiber layer 30, it is possible to prevent the fibers 40 from becoming airborne and to prevent mass loss. mp and md are measured using a precision electronic balance (Mettler Toledo, model XPR2U). Mp is determined from the measured mp and L1. Md is determined from the measured md and L2.

[0082] As shown in Figure 3, when the fiber layer 30 is provided in both the proximal portion 10P and the distal portion 10D of the coil 10, the mass per unit length of the fiber layer 30 provided in the proximal portion 10P of the coil 10 is preferably 1 / 2 or less, more preferably 1 / 3 or less, and even more preferably 1 / 4 or less, of the mass per unit length of the fiber layer 30 provided in the distal portion 10D of the coil 10. The mass per unit length of the fiber layer 30 provided in the proximal portion 10P of the coil 10 may be 1 / 1000 or more, 1 / 500 or more, or 1 / 100 or more, of the mass per unit length of the fiber layer 30 provided in the distal portion 10D of the coil 10. With such an amount of fiber layer 30, the flexibility of the coil 10 is maintained even when applied to the proximal portion 10P of the coil 10, so that the coil 10 can be placed in the knot while ensuring operability.

[0083] Preferably, the mass of the fiber layer 30 per unit length of the coil decreases from the distal end to the proximal end of the coil 10. Preferably, the mass of the fiber layer 30 located in the proximal portion 10P of the coil 10 decreases from the distal end to the proximal end of the coil 10. Preferably, the mass of the fiber layer 30 located in the distal portion 10D of the coil 10 decreases from the distal end to the proximal end of the coil 10.

[0084] Bulk density BD (g / cm³) of fiber layer 30 ３ ) is the basis weight W (g / m ２ ) is the value obtained by dividing by the thickness T (mm). Specifically, the bulk density BDp of the fiber layer 30 arranged in the proximal part 10P of the coil 10 can be determined from the following equations (3) and (4). The bulk density BDd of the fiber layer 30 arranged in the distal part 10D of the coil 10 can be determined from the following equations (5) and (6). BDp = Wp (g / m ２ ) / Tp(mm)...(3) Wp=mp(mg) / Ap(mm ２ )...(4) BDd=Wd(g / m ２ ) / Td(mm)...(5) Wd=md(mg) / Ad(mm ２) ... (6) Here, Wp: basis weight of the fiber layer 30 located in the proximal part 10P of the coil 10, Tp: thickness of the fiber layer 30 located in the proximal part 10P of the coil 10, Ap: area of ​​the fiber layer 30 located in the proximal part 10P of the coil 10, Wd: basis weight of the fiber layer 30 located in the distal part 10D of the coil 10, Td: thickness of the fiber layer 30 located in the distal part 10D of the coil 10, and Ad: area of ​​the fiber layer 30 located in the distal part 10D of the coil 10.

[0085] (Method for measuring the basis weight of the fiber layer) Under standard conditions (temperature 23±2°C, relative humidity 50±5%), the area Ap of the fiber layer 30 located in the proximal part 10P of the coil 10 and the area Ad of the fiber layer 30 located in the distal part 10D of the coil 10 are measured using a straight ruler (manufactured by Shinwa Measuring Instruments Co., Ltd., model number 13005). Next, mp and md are measured using a precision electronic balance (manufactured by Mettler Toledo, model number XPR2U) in the same manner as in "Method for measuring the mass of the fiber layer per unit length of coil". From the measured mp and Ap, the basis weight Wp of the fiber layer 30 located in the proximal part 10P of the coil 10 can be determined. Similarly, from the measured md and Ad, the basis weight Wd of the fiber layer 30 located in the distal part 10D of the coil 10 can be determined.

[0086] (Method for measuring the thickness of the fiber layer) Under standard conditions (temperature 23±2℃, relative humidity 50±5%), the coil 10 with the fiber layer 30 attached is cut along the radial direction y using 1 cm precision nippers (ESD Corporation, model number EA535TA-13) to obtain three test pieces each from the proximal part 10P and the distal part 10D of the coil 10, with a length of 1 cm in the longitudinal direction x of the coil 10. Here, the test pieces obtained from the proximal part 10P of the coil 10 are referred to as B1, B2, and B3, and the test pieces obtained from the distal part 10D of the coil 10 are referred to as C1, C2, and C3. The distal cross-section of each test piece is observed with a microscope (digital microscope) (Keyence Corporation, model number VHX-X1), and the average thickness of the fiber layer 30 in each cross-section is measured. The average thickness is obtained by measuring the thickness of the fiber layer 30 at points equally spaced in the circumferential direction z of the coil 10 and calculating the average of these thicknesses. The equally spaced points can be, for example, 12 points that are 30° apart from each other within the 360° circumferential direction z of the coil 10. For example, the average thickness of the distal cross-section of test piece B1 can be the average of the thicknesses of the fiber layer 30 at 12 points equally spaced in the circumferential direction z of the distal cross-section of test piece B1. The average of the average thicknesses of test pieces B1 to B3 can be taken as the thickness Tp of the fiber layer 30 located in the proximal part 10P of the coil 10, and the average of the average thicknesses of test pieces C1 to C3 can be taken as the thickness Td of the fiber layer 30 located in the distal part 10D of the coil 10.

[0087] Preferably, the bulk density BDp of the fiber layer 30 located in the proximal portion 10P of the coil 10 is smaller than the bulk density BDd of the fiber layer 30 located in the distal portion 10D of the coil 10. By setting the bulk density in this way, the flexibility of the coil 10 is maintained even when applied to the proximal portion 10P of the coil 10, so that the coil 10 can be placed in the knot while ensuring operability.

[0088] The bulk density BDp of the fiber layer 30 located in the proximal portion 10P of the coil 10 may be 0.1 times or more, 0.2 times or more, 0.3 times or more, and may be 0.9 times or less, 0.8 times or less, or 0.7 times or less, of the bulk density BDd of the fiber layer 30 located in the distal portion 10D of the coil 10.

[0089] It is preferable that the bulk density of the fiber layer 30 decreases from the distal end side to the proximal end side of the coil 10. That is, it is preferable that the gaps between the fibers 40 of the fiber layer 30 widen from the distal end side to the proximal end side of the coil 10. From the distal end side to the proximal end side of the coil 10, the bulk density of the fiber layer 30 may decrease stepwise or may decrease gradually.

[0090] It is preferable that the bulk density BDp of the fiber layer 30 disposed in the proximal portion 10P of the coil 10 decreases from the distal end side to the proximal end side of the coil 10. It is preferable that the bulk density BDd of the fiber layer 30 disposed in the distal portion 10D of the coil 10 decreases from the distal end side to the proximal end side of the coil 10.

[0091] The bulk density of the fiber layer 30 is not particularly limited, but it is preferably 10 ng / cm ３ or more, more preferably 50 ng / cm ３ or more, and even more preferably 100 ng / cm ３ or more. Also, the bulk density of the fiber layer 30 is preferably 10,000 ng / cm ３ or less, more preferably 5,000 ng / cm ３ or less, and even more preferably 1,000 ng / cm ３ or less. When the bulk density is 10 ng / cm ３ or more, it becomes easier to hold the amount of the drug necessary for treatment by the fiber layer 30. Also, when the bulk density is 10,000 ng / cm ３ or less, the flexibility of the coil 10 is maintained even when the fiber layer 30 is disposed in the proximal portion 10P of the coil 10, so that the coil 10 can be placed into the tumor while ensuring operability.

[0092] The basis weight of the fiber layer 30 located at the proximal portion 10P of the coil 10 is preferably smaller than the basis weight of the fiber layer 30 located at the distal portion 10D of the coil 10. The basis weight of the fiber layer 30 located at the proximal portion 10P of the coil 10 is preferably 1 / 2 or less, more preferably 1 / 3 or less, and even more preferably 1 / 4 or less, of the basis weight of the fiber layer 30 located at the distal portion 10D of the coil 10. The basis weight per unit length of the fiber layer 30 located at the proximal portion 10P of the coil 10 may be 1 / 50 or more, 1 / 30 or more, or 1 / 10 or more of the basis weight per unit length of the fiber layer 30 located at the distal portion 10D of the coil 10. With a fiber layer 30 of such a basis weight, the flexibility of the coil 10 is maintained even when applied to the proximal portion 10P of the coil 10, so that the coil 10 can be placed in the knot while ensuring maneuverability.

[0093] The basis weight of the fiber layer 30 is not particularly limited, but for example, 100 ng / m ２ Above, 1000ng / m ２ More than 10000ng / m ２ It may be greater than or equal to 1,000,000 ng / m ２ Below, 2500000ng / m ２ Below, 50000ng / m ２ The following is also acceptable.

[0094] The thickness of the fiber layer 30 located in the proximal portion 10P of the coil 10 may be the same as or different from the thickness of the fiber layer 30 located in the distal portion 10D of the coil 10. For example, it is preferable that the thickness of the fiber layer 30 located in the proximal portion 10P of the coil 10 is thinner than the thickness of the fiber layer 30 located in the distal portion 10D of the coil 10. The thickness of the fiber layer 30 located in the proximal portion 10P of the coil 10 is preferably 1 / 2 or less, more preferably 1 / 3 or less, and even more preferably 1 / 4 or less, of the thickness of the fiber layer 30 located in the distal portion 10D of the coil 10. The thickness of the fiber layer 30 located in the proximal portion 10P of the coil 10 per unit length of the coil may be 1 / 50 or more, 1 / 30 or more, or 1 / 10 or more, of the thickness of the fiber layer 30 located in the distal portion 10D of the coil 10 per unit length of the coil. With a fiber layer 30 of this thickness, even if it is applied to the proximal portion 10P of the coil 10, the flexibility of the coil 10 is maintained, allowing the coil 10 to be placed in the nodule while ensuring operability.

[0095] The thickness of the fiber layer 30 is not particularly limited, but may be, for example, 1 μm or more, 5 μm or more, 10 μm or more, or 100 μm or less, 50 μm or less, or 20 μm or less. A fiber layer thickness of 1 μm or more makes it easier to hold the amount of drug necessary for treatment. Also, a fiber layer thickness of 100 μm or less ensures that the flexibility of the coil 10 is maintained even when the fiber layer 30 is placed on the proximal part 10P of the coil 10, so that the coil 10 can be placed in the aneurysm while ensuring maneuverability.

[0096] Hereinafter, the fibers 40 of the fiber layer 30 located in the proximal portion 10P of the coil 10 will be referred to as the proximal portion 10P fibers 40, and the fibers 40 of the fiber layer 30 located in the distal portion 10D of the coil 10 will be referred to as the distal portion 10D fibers 40.

[0097] The polymer material 41 contained in the fiber 40 of the proximal part 10P and the polymer material 41 contained in the fiber 40 of the distal part 10D may be the same or different. For example, the polymer material 41 contained in the fiber 40 of the proximal part 10P may be a biodegradable polymer material, and the polymer material 41 contained in the fiber 40 of the distal part 10D may be a non-biodegradable polymer material. Alternatively, the polymer material 41 contained in the fiber 40 of the proximal part 10P may be a non-biodegradable polymer material, and the polymer material 41 contained in the fiber 40 of the distal part 10D may be a biodegradable polymer material.

[0098] The drug 42 contained in the fiber 40 of the proximal part 10P and the drug 42 contained in the fiber 40 of the distal part 10D may be of the same type or different types.

[0099] It is preferable that the decomposition rate of the fibers 40 in the proximal portion 10P is relatively higher than that of the distal portion 10D. For example, in such a configuration, if the polymer material 41 contained in the fibers 40 of the proximal portion 10P and the polymer material 41 contained in the fibers 40 of the distal portion 10D are of the same type, it is preferable that the mass per coil unit length of the polymer material 41 contained in the fibers 40 of the proximal portion 10P is less than the mass per coil unit length of the polymer material 41 contained in the fibers 40 of the distal portion 10D. In "mass per coil unit length of polymer material 41 contained in the fibers 40 of the proximal portion 10P", "coil unit length" refers to the length L1 described above, and in "mass per coil unit length of polymer material 41 contained in the fibers 40 of the distal portion 10D", "coil unit length" refers to the length L2 described above. The same applies in the following explanation.

[0100] If the fiber 40 is a core-sheath type fiber, the ratio of the cross-sectional area of ​​the sheath portion 45 to the total cross-sectional area of ​​the cross section perpendicular to the longitudinal axis of the fiber 40 is defined as the sheath portion cross-sectional area ratio. If the entire fiber layer 30 is composed of core-sheath type fibers having a core portion 44 and a sheath portion 45, it is preferable that the sheath portion cross-sectional area ratio of the fiber 40 in the proximal portion 10P is smaller than that of the fiber 40 in the distal portion 10D. This makes it easier to change the rate of drug release from the fiber layer 30 between the distal portion 10D and the proximal portion 10P, as the decomposition rate of the fiber 40 in the proximal portion 10P tends to be relatively higher than that of the distal portion 10D.

[0101] The ratio of the sheath cross-sectional area of ​​the fibers 40 in the proximal portion 10P is obtained by measuring the ratio of the sheath cross-sectional area of ​​10 fibers 40, arbitrarily selected from the fiber layer 30 arranged in the proximal portion 10P, at the midpoint of their longitudinal axis, and then calculating the average value of the sheath cross-sectional area ratios of the 10 fibers 40. The cross-sectional image can be observed using a scanning electron microscope or a laser microscope (for example, a scanning transmission electron microscope (STEM-EDX / EELS) HD-2700 manufactured by Hitachi High-Technologies Corporation). The ratio of the sheath cross-sectional area of ​​the fibers 40 in the distal portion 10D can be determined by the same method.

[0102] The biodegradable material contained in the fibers 40 of the proximal portion 10P and the distal portion 10D may be the same type. In that case, it is preferable that the mass of the biodegradable material per unit length of coil contained in the fibers 40 of the proximal portion 10P is greater than the mass of the biodegradable material per unit length of coil contained in the fibers 40 of the distal portion 10D. This configuration also makes it easier to relatively increase the decomposition rate of the fibers 40 of the proximal portion 10P compared to that of the distal portion 10D.

[0103] The non-biodegradable material contained in the fibers 40 of the proximal portion 10P and the distal portion 10D may be the same type. In that case, it is preferable that the mass of the non-biodegradable material contained in the fibers 40 of the proximal portion 10P per unit length of coil is less than the mass of the non-biodegradable material contained in the fibers 40 of the distal portion 10D per unit length of coil. This configuration also makes it easier to relatively increase the decomposition rate of the fibers 40 of the proximal portion 10P compared to that of the distal portion 10D.

[0104] As shown in Figures 1 to 3, the retaining device 1 is positioned proximal to the coil 10 in the longitudinal direction x of the coil 10, and may further include a pusher 55 that pushes the coil 10 distally, and a connecting portion 53 that connects the proximal portion 10P of the coil 10 and the distal portion of the pusher 55.

[0105] The pusher 55 is a rod-shaped or wire-shaped member used to hold the coil 10 and push it distally. The pusher 55 can consist of one or more members. The pusher 55 can consist of a wire member, a coil member, or a combination thereof. The pusher 55 can be made of a conductive material such as stainless steel.

[0106] The connection portion 53 connects the coil 10 and the pusher 55. Preferably, the connection portion 53 has a detachment mechanism that allows the coil 10 to detach from the pusher 55. Examples of detachment mechanisms include hydraulic, electric, and mechanical types, and among these, an electric detachment mechanism is preferred. In the detachment mechanism, it is preferable that the connection portion 53 is heated and disconnected by electrical or thermal energy supplied through the pusher 55, thereby detaching the coil 10 from the pusher 55. In this case, it is preferable that the connection portion 53 is heated by a high-frequency current supplied between the distal end of the pusher 55 and the counter electrode.

[0107] The connecting portion 53 preferably contains a material that melts or dissolves when heated. The connecting portion 53 can be cut by Joule heating. Examples of such materials include synthetic resin materials, and it is preferable to use hydrophilic resins of synthetic polymer substances such as polyvinyl alcohol (PVA), PVA crosslinked polymers, PVA water-absorbing gel freeze-thaw elastomers, and polyvinyl alcohol copolymers.

[0108] The shape of the connecting portion 53 is not particularly limited and may be linear, rod-shaped, cylindrical, polygonal prism-shaped, cylindrical, polygonal tube-shaped, frustoconical, frustoconical, or a combination thereof.

[0109] It is preferable that a portion of the connecting portion 53 is inserted into the lumen 11 of the coil 10, and it is preferable that the distal end of the connecting portion 53 is inserted into the lumen 11 of the coil 10. It is preferable that the proximal end of the connecting portion 53 extends proximally from the proximal end of the coil 10.

[0110] The outer surface of the connecting portion 53 may be in contact with the inner surface 13 of the coil 10, or it may be spaced radially away from the inner surface 13 of the coil 10 in the radial direction y. In addition, a part of the connecting portion 53 may be positioned in the gap between adjacent wires 21 in the longitudinal direction x of the coil 10.

[0111] As shown in Figures 1 to 3, the implantation device 1 may have a tip 25 positioned at the distal end of the coil 10. The tip 25 covers a portion of the wire 21 to prevent the distal end of the wire 21 from directly contacting the inner wall surface of the body. A portion of the tip 25 may be inserted into the lumen 11 of the coil 10. The tip 25 may be in contact with the outer circumferential surface 12 of the coil 10, or it may be in contact with the inner circumferential surface 13 of the coil 10. Preferably, the tip 25 closes off the distal end of the coil 10.

[0112] As shown in Figures 1 to 3, the indwelling device 1 is positioned at the proximal end of the coil 10 and may have a base tip 26 for closing the proximal end of the coil 10. The base tip 26 may be in contact with the outer circumferential surface 12 of the coil 10, or it may be in contact with the inner circumferential surface 13 of the coil 10. The base tip 26 has a lumen, and a part of the connecting portion 53, for example, its distal end, may be inserted into the lumen.

[0113] The tip 25 and / or base tip 26 may be made of a metal material or a resin. Examples of resins include thermoplastic resins and UV-curing resins. For example, ester resins such as epoxy acrylate resins, urethane acrylate resins, polyester acrylate resins, and polyethylene terephthalate resins, and olefin resins such as polypropylene can be used. As for the metal, the metals mentioned in the description of the wire 21 can be used.

[0114] If the retaining device 1 has a pusher 55 and a connecting portion 53, it is preferable that the fiber layer 30 is positioned distal to the distal end of the connecting portion 53, as shown in Figure 3, etc.

[0115] As shown in Figure 3, the retaining device 1 may have a first portion 15 in which the coil 10 and the connecting portion 53 are arranged to overlap in the longitudinal direction x. In the first portion 15, it is preferable that the coil 10 and the connecting portion 53 are fixed together. In the first portion 15, it is preferable that the coil 10 is fixed to the connecting portion 53 via the base end tip 26.

[0116] As shown in Figure 10, it is preferable that the fiber layer 30 is not disposed on the surface of the coil 10 in the first part 15, and it is more preferable that the fiber layer 30 is not disposed on the outer peripheral surface 12 of the coil 10 in the first part 15. Furthermore, it is more preferable that the fiber layer 30 is not disposed on the inner peripheral surface 13 of the coil 10 in the first part 15. If the fiber layer 30 is disposed on the surface of the coil 10 in the first part 15, the bonding strength between the coil 10 and the connection part 53 may become unstable depending on the orientation of the fibers 40, but by not distributing the fiber layer 30 on the surface of the coil 10 in the first part 15, it becomes easier to stably fix the coil 10 and the connection part 53. Note that, as shown in Figure 3, the fiber layer 30 may be disposed on the surface of the coil 10 in the first part 15.

[0117] The position of the proximal end of the first part 15 is the same as the position of the proximal end of the coil 10 in the longitudinal direction x. The position of the distal end of the first part 15 is the same as the position of the distal end of the connection part 53 in the longitudinal direction x. Here, the position of the proximal end of the coil 10 refers to the most proximal position of the coil 10, including parts that are covered and not visible by components such as the tip 25 and the base tip 26. Similarly, the position of the distal end of the coil 10 refers to the most distal position of the coil 10.

[0118] As shown in Figure 10, the in-vivo implantation device 1 may have a first portion 15 and a second portion 16 extending longitudinally from the distal end of the coil 10 to the distal end of the first portion 15. In the second portion 16, it is preferable that a fiber layer 30 is arranged on the surface of the coil 10. In that case, it is preferable that the mass per unit length of the coil of the fiber layer 30 arranged in the second portion 16 is greater than the mass per unit length of the coil of the fiber layer 30 arranged in the first portion 15.

[0119] The distal end of the second section 16 is located at the same position as the distal end of the coil 10 in the longitudinal direction x. The proximal end of the second section 16 is located at the same position as the distal end of the first section 15.

[0120] The mass per unit length of the fiber layer 30 arranged in the first part 15 and the mass per unit length of the fiber layer 30 arranged in the second part 16 can be measured in the same manner as the mass per unit length of the fiber layer 30 arranged in the proximal part 10P or distal part 10D of the coil 10.

[0121] In Figure 3, the second portion 16 is longer than the first portion 15 in the longitudinal direction x.

[0122] As shown in Figure 10, the fiber layer 30 may be distributed over the entire second portion 16, or as shown in Figure 11, the fiber layer 30 may be distributed only over a part of the second portion 16. For example, when the second portion 16 is divided into a distal second portion and a proximal second portion in the longitudinal direction x, the fiber layer 30 may be distributed only over the distal second portion or only over the proximal second portion.

[0123] Hereinafter, the fibers 40 of the fiber layer 30 located in the first part 15 may be referred to as the fibers 40 of the first part 15, and the fibers 40 of the fiber layer 30 located in the second part 16 may be referred to as the fibers 40 of the second part 16.

[0124] The fibers 40 of the first part 15 and the fibers 40 of the second part 16 may be of the same type or different types. For example, the fibers 40 of the first part 15 and the fibers 40 of the second part 16 may contain biodegradable polymer materials but not non-biodegradable polymer materials. The fibers 40 of the first part 15 and the fibers 40 of the second part 16 may contain non-biodegradable polymer materials but not biodegradable polymer materials. The fibers 40 of the first part 15 may contain biodegradable polymer materials but not non-biodegradable polymer materials, and the fibers 40 of the second part 16 may contain non-biodegradable polymer materials but not biodegradable polymer materials. The fibers 40 of the first part 15 may contain non-biodegradable polymer materials but not biodegradable polymer materials, and the fibers 40 of the second part 16 may contain biodegradable polymer materials but not non-biodegradable polymer materials.

[0125] When the biodegradable polymer material contained in the fibers 40 of the first part 15 and the second part 16 is of the same type, it is preferable that the mass of the biodegradable polymer material per unit length of coil contained in the fibers 40 of the first part 15 is greater than the mass of the biodegradable polymer material per unit length of coil contained in the fibers 40 of the second part 16. This makes it easier for the decomposition rate of the first part 15 to be relatively higher than that of the second part 16, thereby allowing the release rate of the drug from the fiber layer 30 to be changed between the first part 15 and the second part 16.

[0126] The non-biodegradable polymer material contained in the fibers 40 of the first part 15 and the second part 16 may be the same type. In that case, it is preferable that the mass per unit length of coil of the non-biodegradable polymer material contained in the fibers 40 of the first part 15 is less than the mass per unit length of coil of the non-biodegradable polymer material contained in the fibers 40 of the second part 16. By configuring the fibers 40 in this way, it becomes easier to make the decomposition rate of the fibers 40 of the first part 15 relatively higher than that of the second part 16.

[0127] As shown in Figures 2 to 3, the fiber layer 30 may be arranged over the entire length x of the coil 10. Since the flexibility of the coil 10 tends to decrease when the fiber layer 30 is provided, the fiber layer 30 may be arranged only in a part of the length x of the coil 10, as shown in Figures 9 to 12. For example, the fiber layer 30 may be arranged in a section of 30% or more of the total length x of the coil 10, or in a section of 40% or more of the total length, or in a section of 50% or more of the total length. Alternatively, the fiber layer 30 may be arranged in a section of 90% or less of the total length x of the coil 10, or in a section of 80% or less of the total length, or in a section of 70% or less of the total length.

[0128] The length of the fiber layer 30 in the longitudinal direction x is preferably the same as or shorter than the length of the coil 10 in the longitudinal direction x. It is preferable that the fiber layer 30 is not located distal to the distal end of the coil 10. Furthermore, it is preferable that the fiber layer 30 is not located proximal to the proximal end of the coil 10.

[0129] As shown in Figures 2 and 3, the entire length x of the coil 10 is covered by the fiber layer 30, and the wire 21 does not need to be exposed.

[0130] As shown in Figure 3, the proximal end 35 of the fiber layer 30 may be positioned more proximal to the distal end of the base tip 26, but as shown in Figures 9 to 11, it is preferable that the proximal end 35 of the fiber layer 30 be positioned more distal to the distal end of the base tip 26. It is preferable that the distal end of the connecting portion 53 be positioned more distal to the distal end of the base tip 26, but the distal end of the connecting portion 53 may be positioned more proximal to the distal end of the base tip 26.

[0131] As shown in Figure 11, it is preferable that the fiber layer 30 is not provided at the distal end of the coil 10. For example, when the wire 21 that is not covered by the tip 25 of the coil 10 and is at the farthest end is counted as the first turn from the distal side of the coil 10, it is preferable that the fiber layer 30 is positioned proximal to the third turn of the coil 10, more preferably proximal to the fifth turn of the coil 10, and even more preferably proximal to the tenth turn of the coil 10. By not providing the fiber layer 30 at the distal end of the coil 10, the outer surface 12 of the coil 10 is more easily exposed at the distal end, which makes it easier for the coil 10 to firmly engage with other parts of the coil and other coils when placed in the knot, and makes it easier to form a framework.

[0132] As shown in Figures 9 to 12 and Figure 16, it is preferable that the fiber layer 30 is not provided at the proximal end of the coil 10. For example, when the wire 21 that is not covered by the base tip 26 and is at the nearest end of the coil 10 is counted as the first turn from the proximal side of the coil 10, it is preferable that the fiber layer 30 is located distal to the third turn of the coil 10, more preferably distal to the fifth turn of the coil 10, and even more preferably distal to the tenth turn of the coil 10. By not providing the fiber layer 30 at the proximal end of the coil 10, the outer circumferential surface 12 of the coil 10 is more easily exposed at the proximal end, which helps to prevent a decrease in the flexibility of the coil 10.

[0133] As shown in Figure 11, it is preferable that the fiber layer 30 is arranged only in the portion of the coil 10 excluding the distal and proximal ends.

[0134] Although not shown in the diagram, the fiber layer 30 may not be provided at the distal end of the coil 10, nor at the proximal portion 10P of the coil 10, and the fiber layer 30 may be provided only in the portion of the coil 10 excluding the distal end and the proximal portion 10P. This makes it easier to engage the distal end of the coil 10 with other members while preventing a decrease in flexibility at the proximal portion 10P of the coil 10.

[0135] As shown in Figures 2, 3, and 10, the distal end 34 of the fiber layer 30 may be positioned distal to the proximal end of the tip 25, but as shown in Figure 11, it is preferable that the distal end 34 of the fiber layer 30 is positioned proximal to the proximal end of the tip 25.

[0136] When the coil has a longitudinal direction x, it is preferable that the fiber 40 is sandwiched between two adjacent wires 21 in the longitudinal direction x, as shown in Figures 12 to 13. By sandwiching the fiber 40 between the wires 21, the drug 42 is less likely to be released from the fiber 40 in the sandwiched portion, thereby improving the sustained release of the drug.

[0137] As shown in Figures 12 to 13, if there is a gap 22 between adjacent wires 21 in the longitudinal direction x, some of the fibers of the fiber layer 30 may be placed in the gap 22. Here, the gap 22 is defined as having a length in the longitudinal direction x that is 1 / 10 or larger than the outer diameter of the wire 21.

[0138] Although not shown in the diagram, even if there is a gap 22 between adjacent wires 21 in the longitudinal direction x, the fiber layer 30 does not need to be placed in the gap 22.

[0139] As shown in Figure 3, the fiber layer 30 may be arranged only on the radially y-outside of the outermost position of the outer peripheral surface 12 of the coil 10.

[0140] Although not shown in the figures, the fiber layer 30 may be positioned radially y-outward from the innermost position of the outer circumferential surface 12 of the coil 10. That is, if the cross-sections of adjacent wires 21 in the longitudinal direction x of the coil 10 are circular, elliptical, etc., the fiber layer 30 may be positioned in the recesses of the uneven structure provided on the surface of the coil 10.

[0141] As shown in Figures 12 to 13, the fiber layer 30 may be positioned radially y inward from the outermost position of the outer peripheral surface 12 of the coil 10.

[0142] As shown in Figure 13, the fiber layer 30 may be arranged on the inner circumferential surface 13 side of the coil 10. That is, the fibers 40 of the fiber layer 30 may be located in the lumen 11 of the coil 10. Since the drug 42 is less likely to be released from the fibers 40 located in the lumen 11 compared to the fibers 40 located on the outer circumferential surface 12, the sustained release of the drug can be improved.

[0143] As can be seen from Figure 13, if there is a gap 22 between adjacent wires 21 in the longitudinal direction x, the fiber layer 30 may enter the lumen 11 of the coil 10 through the gap 22.

[0144] The coil 10 shown in Figure 13 may be formed by providing a fiber layer 30 on the outer surface of a wire 21, and then winding the wire 21 with the fiber layer 30 to form a coil shape.

[0145] Although not shown in the diagram, the second agent may be impregnated into the interfiber gaps of the fiber layer 30. This allows the fiber layer 30 to hold a large amount of the agent while preventing an initial burst of the agent. For the composition of the second agent, please refer to the description of agent 42.

[0146] Although not shown in the figures, in addition to the fiber layer 30, a drug may be placed on the surface of the coil 10. In that case, the drug may be placed on the outer circumferential surface 12 or on the inner circumferential surface 13. The drug placed on the surface of the coil 10 may be held on the surface of the coil 10 as a drug layer. A drug layer may be placed on the outer circumferential surface 12 of the coil 10, and the fiber layer 30 may be placed outside the drug layer in the radial direction y.

[0147] In addition to the fiber layer 30, the agent applied to the coil 10 may be directly attached to the surface of the coil 10, or it may be attached indirectly to the surface of the coil 10 via a bioadhesive. The type of bioadhesive material is not particularly limited, but for example, polysaccharide adhesives such as collagen, chitosan, and gelatin, polyethylene glycol-based hydrogel adhesives, and protein adhesives such as fibrin and collagen can be used.

[0148] If the drug is directly attached to the surface of the coil 10, the drug may be covered by the fiber layer 30 in order to control the rate of drug release.

[0149] In addition to the fiber layer 30, the drug applied to the coil 10 is preferably encapsulated. The drug encapsulated in the capsule may be directly attached to the surface of the coil 10, or it may be attached indirectly to the surface of the coil 10 via a bioadhesive. The size of the capsule is preferably 10 nm or larger, more preferably 50 nm or larger, even more preferably 100 nm or larger, and preferably 500 nm or smaller, more preferably 400 nm or smaller, and even more preferably 200 nm or smaller. The capsule preferably contains a biodegradable material.

[0150] As shown in Figure 3, it is preferable that the retaining device 1 has a stretch resistance member 50 positioned in the lumen 11 of the coil 10. The stretch resistance member 50 suppresses the stretching of the coil 10 in the longitudinal direction x during operation.

[0151] The stretch resistance member 50 may be a long member made of a single wire or stranded wire. The stretch resistance member 50 can be linear, wavy, helical, or a combination thereof. Only one or more stretch resistance members 50 may be placed in the lumen 11. The stretch resistance member 50 may be made of resin or metal.

[0152] The first end of the stretch resistance member 50 may be connected to the distal end of the coil 10 (for example, the distal end of the wire 21). The second end of the stretch resistance member 50 may be connected to the proximal end of the coil 10 (for example, the proximal end of the wire 21) or to the connection part 53. The stretch resistance member 50 may be placed in the lumen 11 in a state where it is folded back in the middle of its longitudinal axis direction.

[0153] Methods for connecting the stretch resistance member 50 to other members include welding, crimping, adhesive bonding, engagement, linking, binding, ligation, and other physical fixing methods, or combinations thereof. Here, "connection" includes both forms in which the two elements are directly connected and forms in which the two elements are indirectly connected through one or more other elements.

[0154] (Second Embodiment) The second embodiment of the in-vivo implantation device according to the present disclosure will be described with reference to Figures 14 to 16. Figure 14 is a cross-sectional view (partially a side view) along the longitudinal direction of the coil of the in-vivo implantation device according to the second embodiment, showing the coil in a straight line. Figures 15 to 16 are side views (partially cross-sectional views) showing modified examples of the in-vivo implantation device shown in Figure 14. The in-vivo implantation device 100 in the second embodiment comprises a coil 10, a first fiber layer 301 containing fibers disposed on the outer peripheral surface 12 of the coil 10, and a second fiber layer 302 containing fibers disposed proximal to the first fiber layer 301 on the outer peripheral surface 12 of the coil 10, wherein the fibers of the first fiber layer 301 and the fibers of the second fiber layer 302 each contain a polymer material and a drug, respectively, and the mass per unit length of the coil of the second fiber layer 302 is less than the mass per unit length of the coil of the first fiber layer 301. In the in-vivo implantation device 100, the fibers of the first fiber layer 301 and the second fiber layer 302 contain the drug, which prevents the drug from detaching from the coil 10 early in the procedure and improves the sustained release of the drug compared to when the drug is coated on the coil surface. Furthermore, in the in-vivo implantation device 100, the mass per unit length of the second fiber layer 302 is less than the mass per unit length of the first fiber layer 301, making it easier to form a rigid portion of the coil 10 where the first fiber layer 301 is located. This makes it easier to use this portion to find empty spaces within the aneurysm and place the coil 10 deep within the aneurysm. As a result, the displacement of the coil 10 from the parent vessel can be suppressed. In addition, the portion of the coil 10 where the second fiber layer 302 is located can be made more flexible than the portion where the first fiber layer 301 is located, making it easier to fold and pack the coil 10 into the aneurysm in the latter half of the implantation procedure.

[0155] The mass M1 per unit length of the coil of the first fiber layer 301 can be expressed by the following equation (7). The mass M2 per unit length of the coil of the second fiber layer 302 can be expressed by the following equation (8). M1 = m1 (mg) / L3 (mm) ... (7) M2 = m2 (mg) / L4 (mm) ... (8) Here, m1: total mass of the first fiber layer 301, L3: total length of the first fiber layer 301 in the longitudinal direction x when the first fiber layer 301 is arranged in the coil 10, m2: total mass of the second fiber layer 302, L4: total length of the second fiber layer 302 in the longitudinal direction x when the second fiber layer 302 is arranged in the coil 10.

[0156] The mass M1 per unit length of the first fiber layer 301 and the mass M2 per unit length of the second fiber layer 302 can be measured by the following method. (Method for measuring the mass M1 per unit length of the first fiber layer 301 and the mass M2 per unit length of the second fiber layer 302) Under standard conditions (temperature 23±2℃, relative humidity 50±5%), the lengths L3 and L4 are measured using a straight ruler (manufactured by Shinwa Measuring Instruments Co., Ltd., model number 13005). At the boundary between the first fiber layer 301 and the second fiber layer 302 in the longitudinal direction x (the midpoint 14 in the longitudinal direction x of the coil 10 in Figure 14), the coil 10 is cut along the radial direction y by 1 cm using precision nippers (ESD Corporation, model number EA535TA-13) to separate the coil 10. The coil 10 on the side with the first fiber layer 301 is designated as test piece D1, and the coil 10 on the side with the second fiber layer 302 is designated as test piece D2. Test piece D1 is immersed in deionized water, and the first fiber layer 301 arranged on the coil 10 is scraped off using a blade such as a razor. By scraping the first fiber layer 301 from the coil 10 in deionized water so as to remove fragments of the fibers 40 of the first fiber layer 301, it is possible to prevent the fibers 40 from floating in the air and to prevent mass loss. The second fiber layer 302 arranged on the coil 10 is scraped off from test piece D2 in the same manner. The total mass m1 of the first fiber layer 301 and the total mass m2 of the second fiber layer 302 are measured using a precision electronic balance (Mettler Toledo, model XPR2U). M1 is determined from the measured m1 and L3. M2 is determined from the measured m2 and L4.

[0157] For details regarding the configuration of the coil 10, please refer to the description of the coil 10 according to the first embodiment.

[0158] Since the second fiber layer 302 is positioned more proximal to the first fiber layer 301, the distal end of the second fiber layer 302 is positioned more proximal to the proximal end of the first fiber layer 301.

[0159] In the longitudinal direction x of the coil 10, the first fiber layer 301 may be the same length as the second fiber layer 302, or it may be longer than the second fiber layer 302. The first fiber layer 301 may also be shorter than the second fiber layer 302.

[0160] It is preferable that both the first fiber layer 301 and the second fiber layer 302 have a cylindrical shape, as shown in Figure 4.

[0161] The first fiber layer 301 is preferably located in the distal portion 10D of the coil 10. The second fiber layer 302 is preferably located in the proximal portion 10P of the coil 10.

[0162] The first fiber layer 301 and the second fiber layer 302 may each be arranged in the distal portion 10D of the coil 10.

[0163] As shown in Figure 14, the first fiber layer 301 and the second fiber layer 302 may be in contact with each other, or they may be spaced apart in the longitudinal direction x, as shown in Figures 15 to 16. When the first fiber layer 301 and the second fiber layer 302 are spaced apart in the longitudinal direction x, the distance between the proximal end of the first fiber layer 301 and the distal end of the second fiber layer 302 is preferably greater than the maximum outer diameter of the wire 21 constituting the coil 10, and may be 2 times or more, 5 times or more, or 20 times or less, 15 times or less, or 10 times or less the maximum outer diameter of the wire 21.

[0164] As shown in Figure 16, the retaining device 100 has a first portion 15 in which the coil 10 and the connecting portion 53 are arranged to overlap in the longitudinal direction x, and it is preferable that the second fiber layer 302 is not arranged on the surface of the coil 10 in the first portion 15.

[0165] The thicknesses of the first fiber layer 301 and the second fiber layer 302 may be the same or different. For example, it is preferable that the thickness of the second fiber layer 302 is thinner than the thickness of the first fiber layer 301. The thickness of the second fiber layer 302 is preferably 1 / 2 or less of the thickness of the first fiber layer 301, more preferably 1 / 3 or less, and even more preferably 1 / 4 or less. The mass of the second fiber layer 302 per unit length of coil may be 1 / 50 or more, 1 / 30 or more, or 1 / 10 or more of the thickness of the first fiber layer 301 per unit length of coil.

[0166] The thickness of the first fiber layer 301 and the second fiber layer 302 is not particularly limited, but may be, for example, 1 μm or more, 5 μm or more, 10 μm or more, or 100 μm or less, 50 μm or less, or 20 μm or less.

[0167] The polymer material 41 contained in the fibers 40 of the first fiber layer 301 and the polymer material 41 contained in the fibers 40 of the second fiber layer 302 may be of the same type or different types.

[0168] The drug 42 contained in the fibers 40 of the first fiber layer 301 and the drug 42 contained in the fibers 40 of the second fiber layer 302 may be of the same type or different types.

[0169] The configuration of the first fiber layer 301 can be referenced to the configuration of the fiber layer 30 arranged in the distal portion 10D of the coil 10 according to the first embodiment.

[0170] The configuration of the second fiber layer 302 can be referenced to the configuration of the fiber layer 30 arranged in the proximal portion 10P of the coil 10 according to the first embodiment.

[0171] For other configurations of the first fiber layer 301 and the second fiber layer 302, refer to the description of the fiber layer 30 arranged in the coil 10 according to the first embodiment.

[0172] The retaining device 100 may have at least one of the following: a tip 25, a base tip 26, an extension resistance member 50, a connecting portion 53, and a pusher 55. The configuration of these components can be appropriately described in the description of the first embodiment.

[0173] This application claims the benefit of priority based on Japanese Patent Application No. 2025-17310, filed on 5 February 2025. The entire specification of Japanese Patent Application No. 2025-17310, filed on 5 February 2025, is incorporated herein by reference.

[0174] 1, 100: Intravivo device 10: Coil 11: Lumen 12: Outer surface 13: Inner surface 14: Midpoint in the longitudinal direction 15: First part 16: Second part 21: Wire 22: Gap 25: Tip 26: Proximal tip 30: Fiber layer 31: Lumen 32: Outer surface 33: Inner surface 34: Distal end 35: Proximal end 40: Fiber 41: Polymer material 42: Drug 44: Core 45: Sheath 50: Stretch resistance member 53: Connection part 55: Pusher 60: Image 301: First fiber layer 302: Second fiber layer p: Longitudinal axis direction of the wire x: Longitudinal direction of the coil y: Radial direction of the coil z: Circumferential direction of the coil

Claims

Coil and, Displaced on the outer surface of the coil, it has a fiber layer containing fibers, The aforementioned fiber contains a polymer material and a drug, An in-vivo implant in which the mass per unit length of the fiber layer disposed in the proximal part of the coil is less than the mass per unit length of the fiber layer disposed in the distal part of the coil, or in which the fiber layer is disposed in the distal part of the coil and the fiber layer is not disposed in the proximal part of the coil. 　 The in-vivo implantation device further comprises a pusher positioned proximal to the coil in the longitudinal direction of the coil and pushing the coil distally, and a connecting portion connecting the proximal portion of the coil and the distal portion of the pusher, The in-vivo device according to claim 1, wherein the fiber layer is positioned distal to the distal end of the connecting portion. 　 The in-vivo implantation device according to claim 2, having a first portion in which the coil and the connecting portion are arranged to overlap in the longitudinal direction, wherein the fiber layer is not arranged on the surface of the coil in the first portion. 　 The in-vivo implantation device has a first portion in which the coil and the connecting portion are arranged to overlap in the longitudinal direction, and a second portion in the longitudinal direction from the distal end of the coil to the distal end of the first portion. The in-vivo implantation device according to claim 2, wherein the mass per unit length of the fiber layer arranged in the second portion is greater than the mass per unit length of the fiber layer arranged in the first portion. 　 Coil and, Displaced on the outer surface of the coil, a first fiber layer containing fibers, The coil has a second fiber layer which is located proximal to the first fiber layer on the outer surface of the coil and includes fibers, The fibers of the first fiber layer and the fibers of the second fiber layer each contain a polymer material and a drug, An in-vivo implant in which the mass per unit length of the second fiber layer is less than the mass per unit length of the first fiber layer. 　 The in-vivo implantation device according to claim 1 or 5, wherein the fiber includes a core-sheath type fiber having a core portion and a sheath portion, the core portion containing the drug, and the sheath portion containing the polymer material. 　 The in-vivo implantation device according to claim 1 or 5, wherein the polymer material is a biodegradable polymer material.

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